Under the direction of Dr. Robert J. Schwartz, the Stem Cell Engineering Laboratory is focused on developing a knowledge base and advanced methods for induced pluripotent stem cell therapy to regenerate heart muscle cells (cardiomyocytes). These efforts will help to identify optimal cell types for such therapy and are designed to overcome technical and ethical issues involved in using embryonic stem cells. Methodology currently under development involves direct transdifferentiation of skin cells into cardiomyocytes. Ultimately, in keeping with THI's mission to completely reconstitute a human heart, the vision is to grow these engineered cells on artificial biomatrices.

Within the department, Dr. Jun Wang leads a team working to understand the molecular and cellular basis of heart development and to identify pathways that lead to cardiomyopathy and congenital heart defects.

Projects

The Stem Cell Engineering Laboratory is focused on the induction of cardiogenic progenitors using novel molecular techniques with the following objectives:

To produce more specialized cells (e.g., cardiac pacemaker cells).

To identify small molecules as catalysts to increase cardiomyocyte production efficiency using specialized drug treatments.

The following achievements represent the current research in the Stem Cell Engineering Laboratory:

Established a research platform to convert human skin-derived cells into cardiomyocytes.

Enhanced fundamental understanding of how cardiomyocytes develop the capacity to beat.

Initiated screening of engineered cells in collaboration with Dr. Edward Yeh's team using novel imaging techniques to track the long-term fate/function of transplanted cells in a mouse heart-attack model.

Dr. Wang's group is focused on understanding how SUMO conjugation affects heart development and function. Recent work from Dr. Wang's lab suggests the importance of balanced SUMO conjugation to heart development; decreased SUMO-1 conjugation in murine hearts caused congenital heart defects, the most common birth defects in the world, and/or cardiomyopathy, the leading cause of death in humans. Ongoing work in Dr. Wang's laboratory seeks to reveal the mechanisms by which SUMO conjugation regulates cardiac development and function.

The following achievements represent the current research in Dr. Wang's laboratory:

Established critical links between sumoylation (a specialized pathway that regulates protein function) and the development of congenital heart defects and cardiomyopathy.

Definitions

Stem cells are unspecialized cells that can multiply through cell division and, being stimulated by appropriate physiologic or experimental conditions, can develop into differentiated cells with tissue- and organ-specific functions.

Induced pluripotent stem (iPS) cells are stem-like cells artificially derived from already specialized cells by inducing a "forced" expression of specific genes so that they acquire potential to develop into other tissue- and organ-specific cells.

Transdifferentiation is a process by which a specialized (differentiated) cell transforms into a different type of specialized cell.

SUMO conjugation, or sumoylation, is a posttranslational modification in which SUMO proteins are covalently and reversibly conjugated to targets, thereby altering the targets' activity.